crossing96/oncoscreening huggingface dataset:
Bladder cancer diagnosis and identification of clinically significant disease by combined urinary detection of Mcm5 and nuclear matrix protein 22.	BACKGROUND: Urinary biomarkers for bladder cancer detection are constrained by inadequate sensitivity or specificity. Here we evaluate the diagnostic accuracy of Mcm5, a novel cell cycle biomarker of aberrant growth, alone and in combination with NMP22. METHODS: 1677 consecutive patients under investigation for urinary tract malignancy were recruited to a prospective blinded observational study. All patients underwent ultrasound, intravenous urography, cystoscopy, urine culture and cytologic analysis. An immunofluorometric assay was used to measure Mcm5 levels in urine cell sediments. NMP22 urinary levels were determined with the FDA-approved NMP22® Test Kit. RESULTS: Genito-urinary tract cancers were identified in 210/1564 (13%) patients with an Mcm5 result and in 195/1396 (14%) patients with an NMP22 result. At the assay cut-point where sensitivity and specificity were equal, the Mcm5 test detected primary and recurrent bladder cancers with 69% sensitivity (95% confidence interval = 62-75%) and 93% negative predictive value (95% CI = 92-95%). The area under the receiver operating characteristic curve for Mcm5 was 0.75 (95% CI = 0.71-0.79) and 0.72 (95% CI = 0.67-0.77) for NMP22. Importantly, Mcm5 combined with NMP22 identified 95% (79/83; 95% CI = 88-99%) of potentially life threatening diagnoses (i.e. grade 3 or carcinoma in situ or stage ≥pT1) with high specificity (72%, 95% CI = 69-74%). CONCLUSIONS: The Mcm5 immunoassay is a non-invasive test for identifying patients with urothelial cancers with similar accuracy to the FDA-approved NMP22 ELISA Test Kit. The combination of Mcm5 plus NMP22 improves the detection of UCC and identifies 95% of clinically significant disease. Trials of a commercially developed Mcm5 assay suitable for an end-user laboratory alongside NMP22 are required to assess their potential clinical utility in improving diagnostic and surveillance care pathways.	bladder
Robotic versus open radical cystectomy: identification of patients who benefit from the robotic approach.	PURPOSE: To identify patients who would benefit from robot-assisted radical cystectomy (RARC), we report perioperative outcomes and complications. PATIENTS AND METHODS: We compared patients who underwent RARC to patients who underwent open cystectomy (OC) in our institution. Data included demographics, operative variables, and recovery. Complications were grouped into early (<30 days), intermediate (31-90 days), and late (>90 days). RESULTS: There were 58 patients in the RARC group and 84 patients in the OC group. The mean age was 66 ± 1.2 years in the RARC v 67 ± 1.2 in OC (p=0.53) group. Women constituted 21% in the RARC and 30% in OC (p=0.23) group. The mean American Society of Anesthesiologists scores were 2.9 for the RARC and 2.94 for OC (p=0.5). The mean operative time for RARC was 7.8 ± 1.5 hours v 6.6 ± 1.25 hours for OC (p<0.0001). Estimated blood loss was 276 ± 48 mL in RARC v 1522 ± 369 mL in OC (p<0.0001). Positive margin rate was 7% in RARC v 8% in OC (p=0.8). Early complications of any severity (Clavien scores) occurred in 43% in RARC and 64% in OC (p=0.02). There was one mortality in RARC and two mortalities in OC. Patients were grouped by age (≥ 70- and <70-years old). The older group consisted of 19 and 44 patients in RARC and OC, respectively. Both age groups in RARC had less early complications than OC patients (p<0.014). The older group in RARC had less early complication rate (17%) than the younger group in OC (59%). CONCLUSIONS: RARC has improved perioperative outcomes with equivalent oncological parameters when compared to open cystectomy. Patients ≥ 70-years old benefit from the robotic approach, particularly when compared to younger patients undergoing open cystectomy.	bladder
[Expression analysis of NOTCH1/HES1/PTEN signaling pathway in invasive bladder transitional cell carcinoma].	OBJECTIVE: To explore the role of NOTCH1/HES1/PTEN signaling pathway in invasive TCCB (bladder transitional cell carcinoma). METHODS: The expressions of NOTCH1, HES1 and PTEN were detected in 36 cases of invasive TCCB tissues and 10 cases of normal bladder samples by real-time q-polymerase chain reaction (q-PCR) and Western blot. Then NOTCH1-ORF plasmid and its blank vector pCMV6-Entry were transfected into T24 cell respectively. And the expressions of three above-mentioned target genes were measured by real-time q-PCR and Western blot. Furthermore, cell proliferation, cell apoptosis and cell cycle were analyzed respectively by MTS assay and flow cytometry. RESULTS: Compared with normal bladder samples, the higher levels of both mRNA and protein of NOTCH1 and HES1 were detected in invasive TCCB tissues while there was a lower expression of PTEN (P < 0.05). The mRNA expression levels of NOTCH1 and HES1 were 4.22 and 3.75 folds respectively higher than those of normal tissues. In NOTCH1-overexpressed T24 cell, the expression of HES1 was 5.43 folds higher than that of the blank vector control group while the expression of PTEN declined to 41.76% (P < 0.01). MTS assay showed that the NOTCH1-ORF transfection obviously promoted cell proliferation in T24 cell (P < 0.01). CONCLUSION: NOTCH1 gene may function as an oncogene by regulating HES1/PTEN in invasive TCCB and its aberrant activation promotes cell proliferation.	bladder
Inflammatory myofibroblastic tumor of the urinary tract following a TVT.	The complications related to the retropubic placement of polypropylene mesh (TVT) for stress urinary incontinence have been extensively described in the literature. The occurrence of an inflammatory myofibroblastic tumor, however, has not been previously reported as a complication of placement of a mesh sling. We report such a case in a patient with neurofibromatosis who had undergone a TVT for stress urinary incontinence and present a brief review of the literature.	bladder
Review: BBN as an urothelial carcinogen.	Experimental urinary bladder tumours have been proposed as a useful model for the study of urinary bladder carcinogenesis, as well as for evaluating new therapeutic strategies. Consequently, the administration of chemical carcinogens is one of the most commonly used methods for inducing urinary bladder tumours. N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is, undoubtedly, the most-used urothelial chemical carcinogen. BBN belongs to the nitrosamine family, a wide group of alkylating agents that are able to induce bladder tumours in laboratory animals. Depending on the animal species, the spectrum of urothelial lesions induced by BBN varies, but is similar to those observed in humans. BBN has a high propensity to induce mutations affecting the expression of genes such as p53, RAS and H19 among others. The aim of this study was to review BBN as a urothelial tumour inducer, taking into consideration its chemical characteristics, properties and spectrum of lesions induced, as well as its possible applications.	bladder
Reduced CD151 expression is related to advanced tumour stage in urothelial bladder cancer.	AIMS: CD151 belongs to the group of tetraspanins and is aberrantly expressed in different tumours and differential expression has been associated with prognosis. The aim of this study was to clarify the relationship of CD151 expression with tumour phenotype and clinical outcome in bladder cancer. METHODS: A bladder cancer tissue microarray containing samples from 686 urothelial bladder cancers was analysed by immunohistochemistry. RESULTS: Membranous CD151 immunostaining was recorded in 409 (66.0%) of 620 analysable cases. High CD151 expression was seen in normal urothelium and in most non-invasive tumours. Low CD151 expression levels were associated with a more unfavourable tumour phenotype. CD151 staining was seen in 71.5% of 284 pTa, 62.1% of 145 pT1 and 60.4% of 187 pT2-4 cancers (p = 0.0033). CD151 staining was detectable in 77.3% of 75 grade 1, 71.1% of 273 grade 2 and 57.7% of 272 grade 3 cancers (p < 0.0001). CD151 expression status was not associated with overall or tumour-specific survival in muscle-invasive cancers (pT2-4), tumour progression in pT1 and recurrences in pTa tumours. CONCLUSION: On the basis of our data we conclude that loss of CD151 may contribute to bladder cancer progression through attenuation of cell adhesion. In clinically defined subgroups CD151 expression does not provide additional prognostic information.	bladder
A microRNA-7 binding site polymorphism in HOXB5 leads to differential gene expression in bladder cancer.	PURPOSE: To investigate the biological function of HOXB5 in human bladder cancer and explore whether the HOXB5 3'-UTR SNP (1010A/G), which is located within the microRNA-7 binding site, was correlated with clinical features of bladder cancer. METHODS: Expression of HOXB5 in 35 human bladder cancer tissues and 8 cell lines were examined using real-time PCR and immunohistochemistry. Next, we explored the biological function of HOXB5 in vitro using cell proliferation, migration and colony formation assays. Using bioinformatics, a SNP (1010A/G) was found located within the microRNA-7 binding site in the 3'-UTR of HOXB5. Real-time PCR was used to test HOXB5 expression affected by different alleles. Finally, multivariate logistic regression analysis was used to determine the relationship between SNP (1010A/G) frequency and clinical features in 391 cases. RESULTS: HOXB5 was frequently over-expressed both in bladder cancer tissues and cell lines. Inhibition of HOXB5 suppressed the oncogenic function of cancer cells. Next, we demonstrated that a SNP (1010A/G), located within the microRNA-7 binding site in the 3'-UTR of HOXB5, could affect HOXB5 expression in bladder cancer mainly by differential binding activity of microRNA-7 and SNP-related mRNA stability. Finally, we also showed the frequency of 1010G genotype was higher in cancer group compared to normal controls and correlated with the risk of high grade and high stage. CONCLUSION: HOXB5 is overexpressed in bladder cancer. A miRNA-binding SNP (1010A/G) located within 3'-UTR of HOXB5 is associated with gene expression and may be a promising prognostic factor for bladder cancer.	bladder
Robotic-assisted laparoscopic radical cystectomy: surgical and oncological outcomes.	PURPOSE: Our first 91 consecutive cases undergoing a robotic assisted cystectomy were analyzed regarding perioperative outcomes, pathological stages and surgical complications. MATERIALS AND METHODS: Between 2007 and 2010 a total of 91 patients (76 male and 15 female), 86 with clinically localized bladder cancer and 5 with non-urothelial tumors underwent a radical robotic assisted cystectomy. We analyzed the perioperative factors, length of hospital stay, pathological outcomes and complication rates. RESULTS: Mean age was 65.6 years (range 28 to 82). Among the 91 patients, 68 were submitted to an ileal conduit and 23 to a neobladder procedure for urinary diversion. Mean operating time was 412 min (range: 243-618 min) and mean blood loss was 294 mL (range: 50-2000 mL). In 29 % of the cases with urothelial carcinoma the T-stage was pT1 or less, 38 % were pT2; 26 % and 7 % were classified as pT3 and pT4, respectively. 14 % of cases had lymph node positive disease. Mean number of lymph nodes removed was 15 (range 4 to 33). Positive surgical margins occurred in 2 cases (2.1 %). Mean days to flatus were 2.13, bowel movement 2.88 and inpatient stay 18.8 (range: 10-33). There were 45 postoperative complications with 11 % major (Clavien grade 3 or higher). At a mean follow-up of 15 months 10 patients had disease recurrence and 6 died of the disease. CONCLUSIONS: Our experience demonstrates that robotic assisted radical cystectomies for the treatment of bladder cancers seems to be very promising regarding surgical and oncological outcomes.	bladder
Laparoscopic radical cystectomy: a 5-year review of a single institute's operative data and complications and a systematic review of the literature.	OBJECTIVE: We aim to evaluate our experience and results with laparoscopic radical cystectomy and conduct a systematic review of studies reporting on 50 or more procedures. MATERIALS AND METHODS: Between February 2006 and March 2011, a prospective study in a single institute on patients with bladder cancer who underwent laparoscopic radical cystectomy was conducted. A search of the Cochrane Library, PubMed, Medline, and Scopus databases was conducted for studies reporting on 50 or more laparoscopic radical cystectomy procedures to compare with our results. RESULTS: Sixty men and five women underwent laparoscopic radical cystectomy during the 5-year study period. Thirty-nine patients were submitted to ileal conduits, 24 to neobladders, and two patients to ureterocutaneostomies. The mean operative time was 294 ± 27 minutes, the mean blood loss was 249.69 ± 95.59 millilitres, the mean length of hospital stay was 9.42 ± 2 days, the mean morphine requirement was 3.69 ± 0.8 days. The overall complication rate was 44.6% (29/65). However, the majority of the patients with complications (90% (26/29)) had minor complications treated conservatively with no further surgical intervention needed. The literature search found seven studies, which reported on their institutions' laparoscopic radical cystectomy results of 50 or more patients. Generally, our results were similar to other reported studies of the same calibre. CONCLUSION: Laparoscopic radical cystectomy is a safe and efficient modality of treatment of bladder cancer. However, it comes with a steep learning curve, once overcome, can provide an alternative to open radical cystectomy.	bladder
Cell-cycle control in urothelial carcinoma: large-scale tissue array analysis of tumor tissue from Maine and Vermont.	BACKGROUND: Cell-cycle proteins are important predictive markers in urothelial carcinoma but may also exhibit exposure-specific heterogeneity. METHODS: Tumor tissue from 491 bladder cancer cases enrolled in the Maine and Vermont component of the New England Bladder Cancer Study was assembled as tissue microarrays and examined for aberrant expression of p53, p63, p16, cyclin D1, Rb, and Ki-67. The association between expression and histopathology, demographics, and cigarette smoking was examined using χ(2) tests, multivariable Poisson, and multinomial regression models. RESULTS: We found that overexpression of p53 and Ki-67 was associated with high-stage/grade tumors [relative risk (RR), 1.26; P(trend) = 0.003; and RR, 3.21; P(trend) < 0.0001, respectively], whereas expression of p63 and p16 was decreased in high-stage/grade tumors (RR, 0.52; P(trend) < 0.0001; and RR, 0.88; P(trend) = 0.04, respectively). No significant aberrations of cell-cycle proteins were identified using various smoking variables and multiple statistical models. CONCLUSION: The results of this population-based study of histologically confirmed urothelial carcinomas show significant aberration of cell-cycle proteins p53, p63, p16, and Ki-67, but not Rb or cyclin D1. p53 showed the most significant heterogeneity with respect to tumor stage and grade, especially when stratified for different staining intensities using novel digital image analysis techniques. Our findings do not support that smoking modifies expression of cell-cycle proteins. IMPACT: Our study shows significant heterogeneity in the expression of key cell-cycle proteins that are associated with disease progression in bladder cancer. Further studies may lead to the identification of biomarkers and their multiplexed interactions as useful prognostic and therapeutic targets.	bladder
Detection of hyaluronidase RNA and activity in urine of schistosomal and non-schistosomal bladder cancer.	Diagnosis of bladder cancer is done by cystoscopy and cytology. In the last decade, many urine-based tests for bladder cancer have been developed and tested in different populations. Hence, it was relevant to assess the diagnostic significance of urinary hyaluronidase RNA and its enzyme activity in bladder cancer. Seventy patients with bladder cancer, 56 patients with benign bladder lesions, and 49 healthy controls were enrolled in this study. Voided urine samples from all subjects were used for estimation of urinary HAase RNA by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and determination of its enzymatic activity by zymography. There was a significant difference in the mean ranks and positivity rates of HAase RNA expression (P < 0.01) and its enzymatic activity among the three investigated groups: malignant, benign, and normal (P < 0.01). In detecting bladder cancer, the sensitivity of urine cytology (42.83 %) was improved to 100 % when combined with urinary Hyal RNA or Hyal enzyme activity. Detection of urinary Hyal RNA and its enzyme activity is promising noninvasive tests with high sensitivities and specificities for detection of bladder cancer.	bladder
Genetic variation in glutathione S-transferase omega-1, arsenic methyltransferase and methylene-tetrahydrofolate reductase, arsenic exposure and bladder cancer: a case-control study.	BACKGROUND: Ingestion of groundwater with high concentrations of inorganic arsenic has been linked to adverse health outcomes, including bladder cancer, however studies have not consistently observed any elevation in risk at lower concentrations. Genetic variability in the metabolism and clearance of arsenic is an important consideration in any investigation of its potential health risks. Therefore, we examined the association between genes thought to play a role in the metabolism of arsenic and bladder cancer. METHODS: Single nucleotide polymorphisms (SNPs) in GSTO-1, As3MT and MTHFR were genotyped using DNA from 219 bladder cancer cases and 273 controls participating in a case-control study in Southeastern Michigan and exposed to low to moderate (<50 μg/L) levels of arsenic in their drinking water. A time-weighted measure of arsenic exposure was constructed using measures from household water samples combined with past residential history, geocoded and merged with archived arsenic data predicted from multiple resources. RESULTS: While no single SNP in As3MT was significantly associated with bladder cancer overall, several SNPs were associated with bladder cancer among those exposed to higher arsenic levels. Individuals with one or more copies of the C allele in rs11191439 (the Met287Thr polymorphism) had an elevated risk of bladder cancer (OR = 1.17; 95% CI = 1.04-1.32 per 1 μg/L increase in average exposure). However, no association was observed between average arsenic exposure and bladder cancer among TT homozygotes in the same SNP. Bladder cancer cases were also 60% less likely to be homozygotes for the A allele in rs1476413 in MTHFR compared to controls (OR = 0.40; 95% CI = 0.18-0.88). CONCLUSIONS: Variation in As3MT and MTHFR is associated with bladder cancer among those exposed to relatively low concentrations of inorganic arsenic. Further investigation is warranted to confirm these findings.	bladder
Associations between toenail arsenic concentration and dietary factors in a New Hampshire population.	BACKGROUND: Dietary factors such as folate, vitamin B12, protein, and methionine are important for the excretion of arsenic via one-carbon metabolism in undernourished populations exposed to high levels of arsenic via drinking water. However, the effects of dietary factors on toenail arsenic concentrations in well-nourished populations exposed to relatively low levels of water arsenic are unknown. METHODS: As part of a population-based case-control study of skin and bladder cancer from the USA, we evaluated relationships between consumption of dietary factors and arsenic concentrations in toenail clippings. Consumption of each dietary factor was determined from a validated food frequency questionnaire. We used general linear models to examine the associations between toenail arsenic and each dietary factor, taking into account potentially confounding effects. RESULTS: As expected, we found an inverse association between ln-transformed toenail arsenic and consumption of vitamin B12 (excluding supplements) and animal protein. Unexpectedly, there were also inverse associations with numerous dietary lipids (e.g., total fat, total animal fat, total vegetable fat, total monounsaturated fat, total polyunsaturated fat, and total saturated fat). Finally, increased toenail arsenic concentrations were associated with increased consumption of long chain n-3 fatty acids. CONCLUSION: In a relatively well-nourished population exposed to relatively low levels of arsenic via water, consumption of certain dietary lipids may decrease toenail arsenic concentration, while long chain n-3 fatty acids may increase toenail arsenic concentration, possibly due to their association with arsenolipids in fish tissue.	bladder
Long-term results of maintenance treatment of mitomycin C or alternating mitomycin C and bacillus Calmette-Guérin instillation therapy of patients with carcinoma in situ of the bladder: a subgroup analysis of the prospective FinnBladder 2 study with a 17-year follow-up.	OBJECTIVE: Only a few studies with a long-term follow-up exist on patients with carcinoma in situ (CIS) treated with instillation therapy. The objective was to study the long-term outcome of patients with CIS after mitomycin C (MMC) monotherapy or alternating therapy with MMC and bacillus Calmette-Guérin (BCG). MATERIAL AND METHODS: The study population comprised 68 patients with CIS belonging to a larger material of 256 patients with non-muscle-invasive bladder carcinoma who were randomized between 1987 and 1992 in a prospective multicentre study. Patients received the same induction period with MMC and continued with maintenance treatment comprising either monthly instillations of MMC alone or alternating MMC and BCG instillations for up to 2 years. Primary endpoints were cancer-specific and overall mortality. Secondary endpoints were time to first recurrence and time to progression. The principal statistical methods were the Kaplan-Meier method and cumulative incidence analysis. RESULTS: The overall median follow-up time of the patients with CIS was 7.2 years and the median follow-up time of the patients still alive was 17.1 years. The non-stratified probability of dying from bladder carcinoma at 5, 10 and 15 years was 13%, 25% and 28%, respectively. No significant difference was found between the study groups with respect to time to first recurrence, progression, or disease-specific or overall mortality. CONCLUSIONS: The long-term bladder cancer-specific mortality was unexpectedly low despite the relatively ineffective instillation therapy and the poor outcome of the patients after progression.	bladder
Chemotherapy sorting can be used to identify cancer stem cell populations.	Cancer stem cells (CSCs) of bladder transitional cell cancers (BTCC) had not been identified by the reported common methods. According to the phenomenon that CSCs were resistant to chemotherapy, BTCC cell lines T24 and 5637 were cultured with mitomycin C respectively. Cell inhibition assay revealed an increased population of drug resistant cancer cells with a concentration gradient of mitomycin C. The maximal and minimal cell inhibition rate in cell line T24 was 92.5 % ± 1.0 versus 64.1 % ± 1.4 (P < 0.001), and in cell line 5637 was 90.2 % ± 2.5 versus 55.1 % ± 1.8 (P < 0.001), respectively. There is no significant difference between these two groups. Drug resistant cells just comprised approximately 7.5 % (T24) versus 9.8 % (5637) of the total cells. Compared with control cells, cell cycle analysis demonstrated that more drug resistant cells were at G0G1 phase and fewer were at S phase with the concentration gradient of mitomycin C in both cell lines, which is in accord with the stem cell theory that most stem cells maintain in a quiescent condition. Importantly, we found that embryonic stem cell markers (OCT-4 and NANOG) were highly expressed in both gene and protein level in BTCC cell line T24 and 5637 after 24-h chemotherapy exposure. Interestingly, the drug concentration gradient was in accord with OCT-4 and NANOG expression, suggesting that chemotherapy sorting might be a feasible method for BTCC CSCs identification.	bladder